7-27202740-A-G

Variant names:

• chr7-27202740-A-G
• rs1859168
• ENST00000472494.2:n.2214A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000472494.2(HOTTIP):​n.2214A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000134 in 148,730 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000013 (0 hom., cov: 22)
• Consequence: HOTTIP ENST00000472494.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.379
• Publications: 40 publications found

Genes affected

HOTTIP (HGNC:37461): (HOXA distal transcript antisense RNA) This gene produces a long RNA in antisense to the HOXA gene cluster. This transcript may regulate expression of HOXA genes in cis. This gene is upregulated in tumors and is implicated in the promotion of cell proliferation. [provided by RefSeq, Dec 2017]

ENSG00000277469 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000472494.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HOTTIP	NR_037843.3		n.2117+102A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HOTTIP	ENST00000472494.2	TSL:2	n.2214A>G		non_coding_transcript_exon	Exon 2 of 2
	HOTTIP	ENST00000521028.4	TSL:5	n.795+102A>G		intron	N/A
	HOTTIP	ENST00000814986.1		n.206+102A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000134 AC: 2 AN: 148730 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000297

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 0

GnomAD4 genome AF: 0.0000134 AC: 2 AN: 148730 Hom.: 0 Cov.: 22 AF XY: 0.0000138 AC XY: 1 AN XY: 72306

African (AFR) AF: 0.00 AC: 0 AN: 40304

American (AMR) AF: 0.00 AC: 0 AN: 14850

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3458

East Asian (EAS) AF: 0.00 AC: 0 AN: 5046

South Asian (SAS) AF: 0.00 AC: 0 AN: 4540

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9940

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 310

European-Non Finnish (NFE) AF: 0.0000297 AC: 2 AN: 67360

Other (OTH) AF: 0.00 AC: 0 AN: 2030

Alfa AF: 0.00 Hom.: 19614

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.7
DANN	Benign	0.77
PhyloP100		-0.38

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1859168; hg19: chr7-27242359;